AiPD: Autoinhibited Protein Database

Q9NRG4

Gene name	SMYD2 (KMT3C)
Protein name	N-lysine methyltransferase SMYD2
Names	EC 2.1.1.- , HSKM-B , Histone methyltransferase SMYD2 , EC 2.1.1.354 , Lysine N-methyltransferase 3C , SET and MYND domain-containing protein 2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:56950
EC number	2.1.1.354: Methyltransferases
Protein Class

Descriptions

SmyD2 belongs to a new class of chromatin regulators that control gene expression in heart development and tumorigenesis. Besides methylation of histone H3 K4, SmyD2 can methylate non-histone targets including p53. The methyltransferase activity of SmyD proteins has been proposed to be regulated by autoinhibition via the intra- and interdomain bending of the conserved C-terminal domain (CTD). The CTD stabilizes the autoinhibited conformation of SmyD2 and restricts access to the catalytic site.<br> In addition, the CTD is structurally similar to tetratricopeptide repeats (TPR), a motif through which many cochaperones bind to the heat shock protein Hsp90. The CTD may be important for the activation of SmyD proteins by Hsp90.

Autoinhibitory domains (AIDs)

280-432 (C-terminal domain containing tetratricopeptide repeats) SS

Target domain	7-241 (SET domain)
Relief mechanism	Partner binding
Assay

AID

280-432 (C-terminal domain containing tetratricopeptide repeats)

Target domain

7-241 (SET domain)

Relief mechanism

Partner binding (Binding of p53 to CTD)

Assay

Accessory elements

No accessory elements

References

Jiang Y et al. (2011) "Crystal structures of histone and p53 methyltransferase SmyD2 reveal a conformational flexibility of the autoinhibitory C-terminal domain", PloS one, 6, e21640

Autoinhibited structure

Activated structure

23 structures for Q9NRG4

Entry ID	Method	Resolution	Chain	Position	Source
3RIB	X-ray	279 A	A/B	1-433	PDB
3S7B	X-ray	242 A	A	1-433	PDB
3S7D	X-ray	230 A	A	1-433	PDB
3S7F	X-ray	285 A	A	1-433	PDB
3S7J	X-ray	304 A	A	1-433	PDB
3TG4	X-ray	200 A	A	1-433	PDB
3TG5	X-ray	230 A	A	1-433	PDB
4O6F	X-ray	282 A	A	1-433	PDB
4WUY	X-ray	163 A	A	1-433	PDB
4YND	X-ray	279 A	A	1-433	PDB
5ARF	X-ray	192 A	A	2-433	PDB
5ARG	X-ray	199 A	A	2-433	PDB
5KJK	X-ray	193 A	A	5-433	PDB
5KJL	X-ray	270 A	A	5-433	PDB
5KJM	X-ray	219 A	A	5-433	PDB
5KJN	X-ray	272 A	A	5-433	PDB
5V3H	X-ray	269 A	A	1-433	PDB
5WCG	X-ray	202 A	A	1-433	PDB
6CBX	X-ray	194 A	A/B	1-433	PDB
6CBY	X-ray	255 A	A/B	1-433	PDB
6MON	X-ray	271 A	A/B	5-433	PDB
6N3G	X-ray	243 A	A	1-433	PDB
AF-Q9NRG4-F1	Predicted				AlphaFoldDB

443 variants for Q9NRG4

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1056140638	2	R>G		No	TOPMed gnomAD
rs1056140638	2	R>W		No	TOPMed gnomAD
rs1298807803	3	A>P		No	gnomAD
rs1298807803	3	A>S		No	gnomAD
rs1365011763	4	E>*		No	TOPMed gnomAD
rs1656435714	4	E>A		No	Ensembl
rs1479754171	4	E>D		No	TOPMed gnomAD
rs1656435714	4	E>G		No	Ensembl
rs1365011763	4	E>K		No	TOPMed gnomAD
rs753255877	6	L>I		No	1000Genomes ExAC TOPMed gnomAD
rs754583820	6	L>R		No	ExAC TOPMed gnomAD
rs753255877	6	L>V		No	1000Genomes ExAC TOPMed gnomAD
rs1656436533	8	G>S		No	TOPMed
rs1308140204	10	E>Q		No	TOPMed
rs1656436707	10	E>V		No	TOPMed
rs1571915369	11	R>C		No	TOPMed
rs1571915369	11	R>G		No	TOPMed
rs757639696	11	R>L		No	1000Genomes ExAC TOPMed gnomAD
rs757639696	11	R>P		No	1000Genomes ExAC TOPMed gnomAD
rs781433570	12	F>S		No	ExAC gnomAD
rs577605405	13	C>Y		No	1000Genomes
rs1656437146	14	S>G		No	TOPMed
rs756551952	14	S>I		No	ExAC gnomAD
rs1483630379	15	P>L		No	TOPMed gnomAD
rs1373617977	18	G>D		No	TOPMed gnomAD
rs1379482355	19	R>Q		No	TOPMed gnomAD
rs1254331821	19	R>W		No	TOPMed gnomAD
rs768793439	21	L>M		No	ExAC gnomAD
rs1656437856	22	R>P		No	Ensembl
rs1417565843	23	A>D		No	Ensembl
COSM1338726	23	A>L	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs544827698	23	A>T		No	1000Genomes gnomAD
rs1417565843	23	A>V		No	Ensembl
rs2102448241	24	L>M		No	Ensembl
rs1656438057	25	Q>*		No	Ensembl
rs774487914	26	P>L		No	ExAC gnomAD
rs1656438116	26	P>S		No	gnomAD
rs1433404752	28	Q>*		No	gnomAD
rs1325891705	28	Q>H		No	TOPMed gnomAD
rs2102448257	29	V>E		No	Ensembl
rs1332198110	29	V>L		No	gnomAD
rs2102448261	30	G>W		No	Ensembl
rs766204493	31	D>E		No	ExAC TOPMed gnomAD
rs760558197	31	D>H		No	ExAC TOPMed gnomAD
rs760558197	31	D>Y		No	ExAC TOPMed gnomAD
TCGA novel	32	L>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1463682066	34	F>L		No	gnomAD
rs1656438852	34	F>L		No	TOPMed
rs1488875703	36	C>S		No	TOPMed
rs759111772	37	P>L		No	ExAC gnomAD
rs752350036	38	A>G		No	ExAC gnomAD
rs140536753	39	Y>C		No	ESP ExAC TOPMed gnomAD
rs1472663157	40	A>D		No	TOPMed gnomAD
rs2102448300	40	A>T		No	Ensembl
rs1472663157	40	A>V		No	TOPMed gnomAD
rs1409346382	41	Y>*		No	gnomAD
rs1656439513	41	Y>C		No	TOPMed
rs1157737917	41	Y>H		No	gnomAD
rs1656439606	43	L>R		No	TOPMed gnomAD
rs1165374808	44	T>M		No	TOPMed gnomAD
rs1386557320	46	N>K		No	TOPMed gnomAD
rs374401037	47	E>D		No	ESP ExAC gnomAD
rs1322208430	47	E>K		No	TOPMed gnomAD
rs201567034	48	R>G		No	1000Genomes ESP ExAC TOPMed gnomAD
rs778981979	48	R>Q		No	ExAC gnomAD
rs201567034	48	R>W		No	1000Genomes ESP ExAC TOPMed gnomAD
rs922228608	49	G>D		No	TOPMed
rs1327360552	49	G>S		No	TOPMed gnomAD
rs372122805	51	H>Y		No	ESP ExAC gnomAD
rs772152951	53	E>D		No	ExAC TOPMed gnomAD
rs951018064	53	E>K		No	TOPMed
rs778105669	54	Y>*		No	ExAC TOPMed gnomAD
rs1355456907	54	Y>C		No	gnomAD
rs1474948828	56	F>I		No	TOPMed
rs1474948828	56	F>L		No	TOPMed
rs770824554	57	T>I		No	ExAC gnomAD
rs776654156	58	R>K		No	ExAC gnomAD
rs776654156	58	R>M		No	ExAC gnomAD
COSM6061369	60	E>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs917770207	60	E>K		No	TOPMed gnomAD
COSM3689341	61	G>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1254846592	61	G>A		No	gnomAD
rs1254846592	61	G>E		No	gnomAD
rs1656897178	62	L>W		No	Ensembl
rs1210283469	63	S>A		No	gnomAD
rs1571924889	63	S>C		No	Ensembl
rs1210283469	63	S>P		No	gnomAD
rs753311770	64	K>E		No	ExAC TOPMed gnomAD
COSM678671	66	G>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1656897427	67	R>G		No	Ensembl
rs746777864	68	C>W		No	Ensembl
rs758341616	69	K>E		No	ExAC TOPMed gnomAD
rs369283055	71	A>S		No	ExAC gnomAD
rs369283055	71	A>T		No	ExAC gnomAD
rs1656897715	72	F>C		No	Ensembl
rs1656897765	73	Y>H		No	TOPMed
rs1279959955	75	N>S		No	TOPMed gnomAD
rs781615758	76	V>A		No	ExAC TOPMed gnomAD
rs757470671	76	V>M		No	ExAC TOPMed gnomAD
rs1656898077	78	C>W		No	TOPMed gnomAD
rs1657053856	80	K>E		No	TOPMed
rs1657053977	82	D>A		No	TOPMed
rs1657053977	82	D>G		No	TOPMed
rs1364152334	83	W>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs1343534465	84	P>S		No	gnomAD
rs767851380	85	M>I		No	ExAC
rs1288379944	85	M>T		No	gnomAD
rs757471509	85	M>V		No	ExAC gnomAD
rs372275852	87	K>E		No	Ensembl
rs1657054389	90	C>R		No	TOPMed
rs1657054493	92	P>A		No	Ensembl
rs755918260	93	M>V		No	ExAC TOPMed gnomAD
rs1323936111	94	V>A		No	TOPMed gnomAD
TCGA novel	95	V>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs779917625	95	V>F		No	ExAC
rs779917625	95	V>I		No	ExAC
rs1222741113	96	F>L		No	gnomAD
rs943912965	97	G>E		No	TOPMed
TCGA novel	97	G>W	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1170967686	98	E>G	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs200744692	98	E>G		No	1000Genomes ExAC TOPMed gnomAD
rs1441351534	99	N>H		No	TOPMed gnomAD
COSM1601635	100	W>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs754909487	100	W>G		No	ExAC TOPMed gnomAD
rs148351602	102	P>L		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1297450926	103	S>L		No	TOPMed gnomAD
rs772782906	106	V>I		No	ExAC gnomAD
rs746676295	109	T>I		No	ExAC TOPMed gnomAD
rs746676295	109	T>R		No	ExAC TOPMed gnomAD
rs770105953	111	R>S		No	ExAC gnomAD
rs763276980	114	A>D		No	ExAC gnomAD
rs763276980	114	A>G		No	ExAC gnomAD
rs867532393	114	A>T		No	Ensembl
rs763276980	114	A>V		No	ExAC gnomAD
rs1368188220	116	Q>E		No	gnomAD
rs554801478	119	H>Q		No	ExAC TOPMed gnomAD
rs768910866	119	H>R		No	ExAC TOPMed gnomAD
rs1657113188	120	P>S		No	Ensembl
rs1558054981	121	E>Q		No	Ensembl
rs147350343	123	T>I		No	ESP ExAC TOPMed gnomAD
rs1199310206	124	P>T		No	TOPMed gnomAD
rs1381115818	125	S>L		No	TOPMed gnomAD
TCGA novel COSM903689	126	E>D	Variant assessed as Somatic; HIGH impact. Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA NCI-TCGA Cosmic
rs1280261387	127	K>*		No	TOPMed
rs1280261387	127	K>E		No	TOPMed
COSM1226915	127	K>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1657113645	128	L>F		No	TOPMed
rs368195995	130	A>G		No	ESP ExAC TOPMed gnomAD
rs894049361	130	A>P		No	TOPMed
rs1657113953	131	V>L		No	TOPMed
rs754074404	132	K>M		No	ExAC TOPMed gnomAD
rs754074404	132	K>R		No	ExAC TOPMed gnomAD
rs1453127256	136	S>L		No	Ensembl
rs759307844	137	H>N		No	ExAC TOPMed gnomAD
TCGA novel rs759307844	137	H>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA ExAC TOPMed gnomAD
rs1320349636	139	D>Y		No	TOPMed gnomAD
rs748560031	142	D>Y		No	ExAC gnomAD
rs376041594	143	N>S		No	ESP ExAC TOPMed gnomAD
rs773909241	146	K>T		No	ExAC TOPMed gnomAD
rs1657127135	150	Q>E		No	TOPMed
rs1657127235	150	Q>H		No	Ensembl
rs1339911898	150	Q>R		No	TOPMed
rs1657127300	152	D>V		No	Ensembl
rs1296450598	153	I>L		No	TOPMed gnomAD
rs1296450598	153	I>V		No	TOPMed gnomAD
rs1657127466	154	A>S		No	gnomAD
rs11550124	157	H>N		No	Ensembl
rs1457388768	157	H>R		No	gnomAD
rs974844297	159	F>L		No	Ensembl
rs1384777995	161	S>C		No	TOPMed gnomAD
rs1384777995	161	S>F		No	TOPMed gnomAD
rs1384777995	161	S>Y		No	TOPMed gnomAD
rs528198800	162	K>R		No	1000Genomes ExAC TOPMed gnomAD
rs369082796	165	G>*		No	ESP ExAC gnomAD
rs1134647	165	G>A		No	1000Genomes ESP ExAC TOPMed gnomAD
VAR_023442 rs1134647	165	G>E		No	UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
COSM903690 rs369082796	165	G>R	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ESP ExAC NCI-TCGA gnomAD
rs61755311	166	F>C		No	1000Genomes ESP ExAC gnomAD
rs1348336252	167	P>L		No	TOPMed gnomAD
rs1348336252	167	P>R		No	TOPMed gnomAD
rs373071843	167	P>S		No	ESP ExAC TOPMed gnomAD
rs1211380465	169	N>S		No	TOPMed gnomAD
rs2102471254	172	L>F		No	Ensembl
rs369877948	173	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP ExAC NCI-TCGA TOPMed gnomAD
rs2102471263	175	L>V		No	Ensembl
rs1657128814	176	F>L		No	TOPMed
rs1657128905	177	A>T		No	Ensembl
rs1657233523	180	N>K		No	TOPMed
rs1657233578	181	C>Y		No	Ensembl
rs1657233801	186	I>T		No	TOPMed
rs1046709986	186	I>V		No	Ensembl
COSM1473385	187	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs778302591	187	E>V		No	ExAC gnomAD
rs747509834	188	D>E		No	ExAC
rs1226089183	190	E>K		No	TOPMed gnomAD
rs2102474710	193	H>L		No	Ensembl
rs1657234088 COSM3483231	193	H>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic TOPMed
rs1249055965	194	L>W	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs2102474725	195	G>E		No	Ensembl
rs757673085	195	G>R		No	ExAC gnomAD
rs1242130183	197	A>V		No	TOPMed gnomAD
rs113133693	198	I>T		No	Ensembl
rs781752596	198	I>V		No	ExAC TOPMed gnomAD
rs1657234625	200	P>A		No	TOPMed
rs1392590984	201	D>N		No	gnomAD
COSM903692	204	L>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1345640203	204	L>W		No	gnomAD
rs1287094343	205	M>T		No	gnomAD
rs750954495	207	H>D		No	ExAC TOPMed gnomAD
rs1657284075	208	S>N		No	Ensembl
rs780140828	209	C>R		No	ExAC gnomAD
rs199700774	209	C>W		No	TOPMed gnomAD
COSM3483232	209	C>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1268352357	211	P>T		No	TOPMed gnomAD
rs755437613	212	N>S		No	ExAC TOPMed gnomAD
rs755437613	212	N>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1215475876	213	V>L		No	gnomAD
rs768846751	214	I>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs781716201	216	T>A		No	Ensembl
rs1657284653	216	T>N		No	TOPMed gnomAD
rs1489727899	217	Y>C		No	gnomAD
rs779249565	218	K>E		No	ExAC gnomAD
TCGA novel	218	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1571933765	218	K>R		No	Ensembl
rs2102476814	219	G>A		No	Ensembl
COSM678670	219	G>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs371305512	220	T>I		No	ESP TOPMed gnomAD
rs747886560	222	A>T		No	ExAC gnomAD
rs771903679	224	V>F		No	ExAC TOPMed gnomAD
rs771903679	224	V>I		No	ExAC TOPMed gnomAD
rs1657285135	227	V>I		No	TOPMed
rs1657285135	227	V>L		No	TOPMed
rs866032840	228	Q>*		No	TOPMed gnomAD
rs1657285335	228	Q>H		No	TOPMed
rs866032840	228	Q>K		No	TOPMed gnomAD
rs1449160528	228	Q>R		No	TOPMed gnomAD
rs760710296	231	K>Q		No	ExAC TOPMed gnomAD
rs1657285444	231	K>T		No	TOPMed
rs140909791	232	P>L		No	1000Genomes ESP ExAC TOPMed gnomAD
rs140909791	232	P>R		No	1000Genomes ESP ExAC TOPMed gnomAD
rs375997509	232	P>S		No	ESP TOPMed gnomAD
rs764794193	235	E>G		No	ExAC gnomAD
rs1425329978	235	E>K		No	gnomAD
rs200797676	237	F>L		No	ExAC TOPMed gnomAD
rs1657328052	238	T>S		No	Ensembl
rs1239405903	239	S>N		No	gnomAD
rs1657328294	241	I>T		No	Ensembl
rs1355012130	245	Y>C		No	gnomAD
rs1314856700	245	Y>H		No	gnomAD
rs1418260200	246	P>L		No	TOPMed gnomAD
rs1657328746	246	P>S		No	TOPMed
rs372313690	247	T>K		No	ESP ExAC TOPMed gnomAD
rs372313690	247	T>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP ExAC NCI-TCGA TOPMed gnomAD
rs1657329008	249	D>H		No	TOPMed
rs1453879180	250	R>T		No	gnomAD
rs745823948	253	R>G		No	ExAC TOPMed gnomAD
rs769148140	253	R>Q		No	ExAC TOPMed gnomAD
rs745823948	253	R>W		No	ExAC TOPMed gnomAD
rs1657329789	255	R>T		No	TOPMed gnomAD
COSM3803839	256	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1571935059	257	S>C		No	Ensembl
rs1571935059	257	S>Y		No	Ensembl
rs775036371	258	Y>*		No	ExAC TOPMed gnomAD
rs1338877658	258	Y>N		No	TOPMed gnomAD
rs921712526	259	F>V		No	Ensembl
rs748800686	261	T>I		No	ExAC gnomAD
rs1657330142	261	T>S		No	Ensembl
rs768344398	262	C>*		No	ExAC TOPMed gnomAD
rs768344398	262	C>W		No	ExAC TOPMed gnomAD
rs1657330370	263	E>K		No	Ensembl
rs1240971361	265	Q>*		No	TOPMed gnomAD
rs774061282	265	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs138767186	267	C>G		No	ESP ExAC TOPMed gnomAD
rs138767186	267	C>R		No	ESP ExAC TOPMed gnomAD
TCGA novel	269	T>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1657330701	271	D>N		No	TOPMed
rs1657342193	274	K>T		No	Ensembl
rs776947435	275	A>V		No	ExAC TOPMed gnomAD
rs770319853	277	V>M		No	ExAC TOPMed gnomAD
TCGA novel	278	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs568105061	279	I>T		No	Ensembl
rs373625174	280	R>Q		No	ESP ExAC TOPMed gnomAD
rs1281666440	280	R>W		No	TOPMed gnomAD
rs1455510092	282	L>V		No	TOPMed gnomAD
rs146944968	283	S>R		No	ESP ExAC TOPMed gnomAD
rs943544949	284	D>N		No	TOPMed gnomAD
COSM331168 rs943544949	284	D>Y	lung [Cosmic]	No	cosmic curated TOPMed gnomAD
rs1348462312	285	P>S		No	gnomAD
rs1194872391	286	P>L		No	Ensembl
rs762098187	286	P>S		No	ExAC TOPMed gnomAD
rs767902423	287	K>N		No	ExAC TOPMed gnomAD
rs1657343073	290	A>P		No	Ensembl
rs541184854	291	I>V		No	ExAC TOPMed gnomAD
rs755932225	292	R>*		No	ExAC gnomAD
rs200752340	292	R>Q		No	1000Genomes ExAC TOPMed gnomAD
rs1657343352	293	D>H		No	Ensembl
rs1055734657	294	M>I		No	Ensembl
rs201570286	294	M>R		No	TOPMed gnomAD
rs201570286	294	M>T		No	TOPMed gnomAD
rs1657343923	296	R>K		No	TOPMed
rs753727813	297	Y>*		No	ExAC gnomAD
rs1558058287	298	A>V		No	Ensembl
COSM903695 rs1468913646	299	R>C	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed gnomAD
rs778423679	299	R>H		No	ExAC TOPMed gnomAD
rs1275631208	300	N>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed
rs747695541	300	N>S		No	ExAC gnomAD
rs141612441	301	V>I		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1398926841	302	I>F		No	gnomAD
rs923414235	302	I>T		No	TOPMed
rs1657344523	303	E>K		No	TOPMed
rs770067918	305	F>L		No	ExAC gnomAD
rs776017737	306	R>Q		No	ExAC TOPMed gnomAD
COSM1338729 rs887231491	306	R>W	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed gnomAD
rs1657344858	307	R>K		No	Ensembl
rs150595452	307	R>S		No	ESP ExAC gnomAD
rs1657344967	309	K>*		No	Ensembl
rs1657344967	309	K>Q		No	Ensembl
rs774552919	311	Y>C		No	ExAC gnomAD
TCGA novel	311	Y>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1657345086	312	K>R		No	TOPMed
rs201487916	314	P>A		No	1000Genomes ExAC gnomAD
rs867430691	315	S>G		No	Ensembl
rs780252872	315	S>T		No	ExAC gnomAD
COSM1295856	319	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs769275348	322	E>*		No	ExAC gnomAD
rs1055699705	322	E>A		No	TOPMed gnomAD
rs1055699705	322	E>G		No	TOPMed gnomAD
rs769275348	322	E>K		No	ExAC gnomAD
rs772296667	325	Q>H		No	ExAC gnomAD
rs748175763	325	Q>P		No	ExAC gnomAD
rs773431617	327	K>N		No	ExAC TOPMed gnomAD
rs963873702	327	K>T		No	TOPMed
rs1347013068	327	K>missing	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1323323505	328	M>I		No	gnomAD
rs760834330	328	M>K		No	ExAC TOPMed gnomAD
rs760834330	328	M>R		No	ExAC TOPMed gnomAD
rs760834330	328	M>T		No	ExAC TOPMed gnomAD
rs766661501	329	S>G		No	ExAC TOPMed gnomAD
rs776266188	329	S>N		No	ExAC gnomAD
rs766661501	329	S>R		No	ExAC TOPMed gnomAD
rs973721636	330	S>F		No	TOPMed gnomAD
TCGA novel	332	F>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1657364710	334	D>N		No	TOPMed
rs1200482699	335	S>G		No	gnomAD
rs1383732834	337	V>A		No	TOPMed gnomAD
rs765154080	337	V>M		No	ExAC TOPMed gnomAD
rs1657365116	339	M>L		No	Ensembl
rs752635538	339	M>T		No	ExAC TOPMed gnomAD
rs1657365243	341	H>Y		No	TOPMed gnomAD
rs1345729969	342	M>I		No	gnomAD
rs757855784	342	M>T		No	ExAC
COSM2151411	344	Y>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	346	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1657365443	347	M>I		No	TOPMed gnomAD
rs1452886202	347	M>V		No	TOPMed gnomAD
rs766703409	348	G>S		No	TOPMed
rs1657365543	348	G>V		No	TOPMed gnomAD
rs200825251	349	V>A		No	1000Genomes ExAC TOPMed gnomAD
rs1469611234	350	C>S		No	gnomAD
rs1558058653	351	L>F		No	Ensembl
rs1657365851	352	Y>C		No	TOPMed gnomAD
rs1282276586	353	M>I		No	gnomAD
rs1404994649	353	M>T		No	TOPMed gnomAD
rs1419309224	353	M>V		No	TOPMed gnomAD
rs1472233174	357	E>K		No	TOPMed
rs751122379	358	G>R		No	ExAC TOPMed gnomAD
rs535733694	359	A>S		No	Ensembl
rs1657366252	359	A>V		No	Ensembl
rs2102479884	361	Q>K		No	Ensembl
rs749669555	362	Y>F		No	ExAC gnomAD
rs755402563	363	G>A		No	ExAC gnomAD
rs1275067168	366	I>M		No	TOPMed gnomAD
rs1223269845	367	I>V		No	gnomAD
rs1268478906	369	P>A		No	gnomAD
rs1487597648	369	P>H		No	gnomAD
rs1487597648	369	P>L		No	gnomAD
rs1408529441	371	S>G		No	gnomAD
rs779044545	371	S>N		No	ExAC TOPMed gnomAD
rs771049277	373	H>Q		No	ExAC gnomAD
rs1657400795	373	H>R		No	TOPMed
rs1377136047	374	Y>*		No	gnomAD
rs770042450	376	L>F		No	ExAC TOPMed gnomAD
rs1196529681	379	L>V		No	gnomAD
rs1657401237	380	N>S		No	TOPMed
rs768471404	381	V>M		No	ExAC TOPMed gnomAD
rs1657401404	382	A>G		No	Ensembl
rs373951400	384	M>I		No	ESP TOPMed gnomAD
rs767072449	384	M>K		No	ExAC gnomAD
rs34259050	384	M>L		No	1000Genomes ESP ExAC TOPMed gnomAD
rs34259050	384	M>V		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1262544497	385	W>*		No	TOPMed gnomAD
rs750064429	385	W>R		No	ExAC gnomAD
rs1657401986	392	Y>C		No	Ensembl
rs1280349293	392	Y>H		No	TOPMed gnomAD
rs767604488	393	M>I		No	Ensembl
rs1198861343	393	M>T		No	gnomAD
rs760376670	393	M>V		No	ExAC TOPMed gnomAD
rs141849218	394	G>C		No	1000Genomes ESP ExAC TOPMed gnomAD
rs367808431	395	L>V		No	ESP ExAC TOPMed gnomAD
TCGA novel	396	E>D	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs778076664	397	H>D		No	ExAC TOPMed gnomAD
rs778076664	397	H>N		No	ExAC TOPMed gnomAD
rs1657402538	398	K>R		No	TOPMed gnomAD
rs1334133050	399	A>D		No	gnomAD
rs752121860	400	A>S		No	ExAC TOPMed gnomAD
rs752121860	400	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs561139349	401	G>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	1000Genomes ExAC NCI-TCGA gnomAD
rs745995313	402	E>K		No	ExAC TOPMed gnomAD
rs745995313	402	E>Q		No	ExAC TOPMed gnomAD
rs2102481251	403	K>N		No	Ensembl
rs2102481248	403	K>T		No	Ensembl
rs1657402933	404	A>T		No	TOPMed
rs1657403015	405	L>Q		No	TOPMed
rs780319511	407	K>N		No	ExAC gnomAD
rs1657403072	407	K>R		No	TOPMed
rs768069244	408	A>V		No	ExAC TOPMed gnomAD
rs1269167890	409	I>M		No	gnomAD
rs1208997094	409	I>T		No	TOPMed gnomAD
rs756188494	409	I>V		No	ExAC gnomAD
rs749543193	411	I>V		No	ExAC gnomAD
rs1376338119	412	M>V		No	gnomAD
rs1657445564	414	V>I		No	TOPMed
rs1657445564	414	V>L		No	TOPMed
rs778741699 COSM463917	417	G>S	lung kidney Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs747946052	418	K>E		No	ExAC
rs772125152	418	K>R		No	ExAC TOPMed gnomAD
rs1386491029	419	D>G		No	gnomAD
rs1366434510	419	D>N		No	TOPMed gnomAD
rs1366434510	419	D>Y		No	TOPMed gnomAD
rs1321815783	420	H>R		No	gnomAD
rs150328399	422	Y>C		No	ESP ExAC TOPMed gnomAD
rs150328399	422	Y>S		No	ESP ExAC TOPMed gnomAD
rs770579884	423	I>V		No	ExAC gnomAD
rs370098014	425	E>K		No	ESP ExAC TOPMed gnomAD
rs759264764	428	Q>*		No	ExAC gnomAD
rs759264764	428	Q>E		No	ExAC gnomAD
rs1657446662	428	Q>P		No	TOPMed gnomAD
rs984688341	429	E>K		No	TOPMed gnomAD
VAR_052991 rs11120301	430	I>M		No	UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1657447059	431	E>Q		No	TOPMed gnomAD
rs1657447117	432	S>R		No	TOPMed
rs774764320	433	H>L		No	ExAC TOPMed gnomAD
rs774764320	433	H>R		No	ExAC TOPMed gnomAD

No associated diseases with Q9NRG4

3 regional properties for Q9NRG4

Type	Name	Position	InterPro Accession
domain	SET domain	7 - 247	IPR001214
domain	Zinc finger, MYND-type	52 - 90	IPR002893
domain	SMYD2, SET domain	7 - 269	IPR044419

Functions

		Description
EC Number	2.1.1.354	Methyltransferases
Subcellular Localization	Cytoplasm, cytosol Nucleus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

8 GO annotations of molecular function

Name	Definition
histone H3 methyltransferase activity	Catalysis of the reaction
histone H3K36 methyltransferase activity	Catalysis of the reaction
histone H3K4 trimethyltransferase activity	Catalysis of the reaction
lysine N-methyltransferase activity	Catalysis of the transfer of a methyl group from S-adenosyl-L-methionine to the epsilon-amino group of a lysine residue.
metal ion binding	Binding to a metal ion.
p53 binding	Binding to one of the p53 family of proteins.
protein-lysine N-methyltransferase activity	Catalysis of the transfer of a methyl group from S-adenosyl-L-methionine to the epsilon-amino group of a lysine residue in a protein substrate.
RNA polymerase II complex binding	Binding to an RNA polymerase II core enzyme, a multisubunit eukaryotic nuclear RNA polymerase typically composed of twelve subunits.

7 GO annotations of biological process

Name	Definition
heart development	The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
negative regulation of cell population proliferation	Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of transcription by RNA polymerase II	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
peptidyl-lysine dimethylation	The methylation of peptidyl-lysine to form peptidyl-N6,N6-dimethyl-L-lysine.
peptidyl-lysine monomethylation	The methylation of peptidyl-lysine to form peptidyl-N6-methyl-L-lysine.
regulation of DNA damage response, signal transduction by p53 class mediator	Any process that modulates the frequency, rate or extent of the cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage.
regulation of signal transduction by p53 class mediator	Any process that modulates the frequency, rate or extent of signal transduction by p53 class mediator.

13 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q0P585	SMYD2	N-lysine methyltransferase SMYD2	Bos taurus (Bovine)	SS
Q5ZIZ2	SMYD5	Histone-lysine N-trimethyltransferase SMYD5	Gallus gallus (Chicken)	PR
E1C5V0	SMYD2	N-lysine methyltransferase SMYD2	Gallus gallus (Chicken)	SS
Q6GMV2	SMYD5	Histone-lysine N-trimethyltransferase SMYD5	Homo sapiens (Human)	PR
Q9H7B4	SMYD3	Histone-lysine N-methyltransferase SMYD3	Homo sapiens (Human)	EV
Q3TYX3	Smyd5	Histone-lysine N-trimethyltransferase SMYD5	Mus musculus (Mouse)	PR
Q9CWR2	Smyd3	Histone-lysine N-methyltransferase SMYD3	Mus musculus (Mouse)	SS
Q8R5A0	Smyd2	N-lysine methyltransferase SMYD2	Mus musculus (Mouse)	EV
C3RZA1	SMYD2	N-lysine methyltransferase SMYD2	Sus scrofa (Pig)	SS
Q7M6Z3	Smyd2	N-lysine methyltransferase SMYD2	Rattus norvegicus (Rat)	SS
P34318	set-3	SET domain-containing protein 3	Caenorhabditis elegans	PR
Q5RGL7	smyd2b	N-lysine methyltransferase SMYD2-B	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q5BJI7	smyd2a	N-lysine methyltransferase SMYD2-A	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MRAEGLGGLE	RFCSPGKGRG	LRALQPFQVG	DLLFSCPAYA	YVLTVNERGN	HCEYCFTRKE
70	80	90	100	110	120
GLSKCGRCKQ	AFYCNVECQK	EDWPMHKLEC	SPMVVFGENW	NPSETVRLTA	RILAKQKIHP
130	140	150	160	170	180
ERTPSEKLLA	VKEFESHLDK	LDNEKKDLIQ	SDIAALHHFY	SKHLGFPDND	SLVVLFAQVN
190	200	210	220	230	240
CNGFTIEDEE	LSHLGSAIFP	DVALMNHSCC	PNVIVTYKGT	LAEVRAVQEI	KPGEEVFTSY
250	260	270	280	290	300
IDLLYPTEDR	NDRLRDSYFF	TCECQECTTK	DKDKAKVEIR	KLSDPPKAEA	IRDMVRYARN
310	320	330	340	350	360
VIEEFRRAKH	YKSPSELLEI	CELSQEKMSS	VFEDSNVYML	HMMYQAMGVC	LYMQDWEGAL
370	380	390	400	410	420
QYGQKIIKPY	SKHYPLYSLN	VASMWLKLGR	LYMGLEHKAA	GEKALKKAIA	IMEVAHGKDH
430
PYISEIKQEI	ESH